CALM, calmodulin, molecular structure, change in conformation upon binding of four Ca2+ ions, interaction with Camk2a, Mylk2 and Kcnn2, calcium

CAMK, Ca2+/calmodulin protein kinase, molecular structure of hub, linker and kinase domain, schematic representation of the assembly into a multiprotein complex, control of kinase activity by Ca2+-oscillations, calcium

Protein kinase C, PKC, classical and novel, family members, molecular structure of domains, priming of the protein kinase through phosphorylation of the AGC-tail by mTORC2 (co-translational), and through phosphorylation of the activation segment by PDK1 (3-phosphoinositide-dependent protein kinase), comparison of conserved phosphorylation sites and phosphosite sequence logo of PRKCA substrates PKCalpha)

ITGA, ITGB (alpha and beta integrin), integrin, adhesion, domain architecture, family members, molecular structure(ITGAV, ITGB3), dimer combinations of ∝- and β-integrin, activation mechanism (switch blade), role of F3-domain of TLN1 in changing the position of the transmembrane segment of β-integrin binding to TLN1.

composition of bacterial cell walls, Gram-positive, negative and mycobacteria, lipopolysaccharides acting as a shield and a pathogen-associated molecular-pattern, PAM, which acts as a ligand for the TLR4 receptor on dendritic cells

LPS-mediated receptor dimerization and assembly of large signaling complexes through assembly of DD-domain carrying proteins (MYD88, IRAK4 and IRAK1), lipopolysaccharide

signaling complex formation through K63-connected ubiquitin chains, role of the TRAF6 E3-ubiquitin ligase complex, binding of TAB2 associated with MAP3K7 (Tak1), and of IKBKG (Nemo) associated with IKBKB (IKKβ) and CHUK (IKK∝), ubiquitinylation

phosphorylation of NFKBIA (inhibitor of κB), recognition by the SCFBTRC E3-ubiquitin ligase complex, K48-ubiquitination, destruction by the proteasome, nuclear localization of NFKB (NFkappaB) and induction of gene transcription

CXCL1 (Gro), CXCR2 (IL8RB) and activation of PLCB2, formation of diacylglycerol, activation of RASGRP2 (guanine nucleotide exchange factor), loading of GTP on RAP1A, leading to membrane recruitment of RASSF5, APBB1IP, and talin-mediated activation of integrins, binding to ICAM1 and arresting the cell on the surface of vascular endothelium

recruitment of phosphatidylinositol 3-kinases (PIK3C) and production of phosphatidylinositol-3,4,5-phosphate,

recruitment of PDK1 and AKT2 through their PH-domain. Formation of a transient kinase dimer followed by transphosphorylation (in activation segment) and activation of AKT2 (PKBbeta), phosphoinositide-dependent protein kinase

phosphorylation and inhibition of GSK3B, activation of glycogen synthase (GYS) and phosphorylation and inhibition of TSC2 (GTPase activating protein), accumulation of the monomeric GTPase RHEB in its GTP-bound state at the lysosomal membrane, activation of the mTORC1 complex in the presence of RRAGA/B bound to GTP and RRAGC/D bound to GDP (permissive condition, only occurs in the presence of sufficient amino-acids in the lysosome), tuberous sclerosis, tuberin, ras-related GTP-binding protein

mTORC1 phosphorylation and activation of RPS6KB1 and phosphorylation and inhibition of 4EBP1 (removed from EIF4E, bound to the mRNA 5’cap, stimulation of protein synthesis), mammalian target of rapamycin, MTOR

5’AMP-mediated activation or PRKAA2 (AMPK), with the help of STK11, phosphorylation and activation of TSC2, accumulation of RHEB in GDP-bound state, enhanced autophagy and reduced protein synthesis

AGC-kinases, members, their domain architecture and common priming and activation mechanism

type 1 and type-2 receptor, phosphorylation of GS-domain, removal of inhibitory wedge, kinase activation, role or ZFYVE9 (SARA) in bringing SMAD to the receptor

SMAD types, receptor-regulated, common mediator and inhibitory, phosphorylation of regulated SMAD protein by type-1 receptor, association with common mediator SMAD4, translocation to the nucleus, binding to SMAD-binding element

phosphorylation of linker region determines duration of transcriptional activity, role of kinases CDK8, CDK9 and phosphatase PPM1A and the RNA-polymerase-associated phosphatases CTDSP1, CTDSP2 and CTDSPL, regulation of protein half-life by phosphorylation through the kinase GSK3B

mono-ubiquitination dissociates SMAD complexes, role of TRIM33/UBE2D3, polyubiquitination (K48) causes destruction, role of NEDD4L and SMURF1

phosphorylation of linker region in cytoplasm prevents nuclear translocation, role of MAPkinase, and promotes destruction, role of SMURF1

holding the pathway in check, role of inhibitory SMAD proteins, SMAD6 in creating inactive SMAD complexes, SMAD7 in blocking the receptors, and causing their uptake and destruction (SMURF2/SMAD7 complex)

bone-morphogenetic protein (BMP, member of the TGFB family) and fibroblast growth factor (FGF) in the induction of neuro-ectoderm in the Xenopus laevis embryo (Spemann organizer activity).

TGFβ and inhibition of cell division cycle progression, SMAD mutations and cancer, role of TGFβ in epithelial mesenchymal transition (EMT)

PTPN1 (PTP1B) in diabetes and obesity, inhibition of insulin signaling, dephosphorylation of receptor and IRS1, inhibitors of PTPN1 avoid insulin resistance, at the level of glucose transport in muscle and liver as well as at the level of POMC transcription in neurons of the arcuate nucleus involved in the inhibition of appetite (anorexigenic signal)

redox regulation of PTPN1, reactive oxygen species (ROS), hydrogen peroxide, thiolate, H2O2-mediated formation of a cyclic sulphonamide that inhibits phosphatase activity leading to amplification of insulin and growth factor signaling

SH2-domain-containing phosphatases, PTPN6 (SHP-1) and PTPN11 (SHP-2), their regulation through binding of SH2-domains to tyrosine phosphorylated proteins, the role of PTPN6 in the attenuating the inflammatory response, loss-of-function causes severe skin inflammation, the role of PTPN11 in boosting the RAS-MAPkinase pathway, gain-of-function mutations of the latter phosphatase cause the Noonan and LEOPARD syndrome and are associated with leukaemia

receptor-like tyrosine phosphatases PTPRF (LAR), PTPRD and PTPRS are adhesion molecules, recognize multiple ligands and the interaction between the two plays a key role in the establishment and subsequent maturation of the neuronal synapse, signaling role still undetermined

dual specificity phosphatases, domain architecture of family members (classified as subfamily of PTP)

Notch pathway employing Nicd, RBPJ, MAML1 and EP300 and leading to transcription of HES and HEY genes

Morgan, the notched wings of Drosophila and the gene theory

domain architecture of NOTCH2 and its ligands (JAG1, DLL1)

description of the cleavage sites, S1 (furin), S2 (ADAM17) and S3 (ɣ-secretase complex) in the extracellular membrane-proximal segment, role of S2 and S3 in the signaling mechanism of NOTCH

cleavage of the S3-site liberates the intracellular segment, Nicd, which translocates into the nucleus, binds the transcription factor RBPJ, an event that leads to the loss of transcriptional repressors (NCOR2, HDAC1)and recruitment of transcriptional activators such as EP300 and the mediator complex.

description of Ncid destruction through phosphorylation of the PEST motif (at C-terminal) by CDK8 followed by its recognition by the E3-ubiquitin ligase SCFFBXW7, multi-ubiquitination (K48), recognition by proteasome

endocytosis is essential for notch signaling in Drosophila, both ligand (delta) and receptor (notch), description of proteins involved in uptake of both (itch, nedd4, lap, numb, shibire (dynamin), mib1 and adaptor-protein-2 complex)

description of imaginal discs of the 3rd instar larva and the corresponding body parts of the adult fly, focus on the wing imaginal disc

description of the mechanoreceptor on thorax and wing, part of the bristle-containing sensory organ. Notch signaling in the sensory organ precursor (SOP) gives rise to two cell types (pIIa and pIIb), each with distinct fates (socket and shaft versus sheath, neuron and glia cell)

description of intestinal stem cell compartment, expression of NOTCH1 in the cycling crypt-base columnar cells (Lgr5+ stem cells) and expression of DLL4 in the adjacent Paneth cells, NOTCH1-mediated expression of HES1 leads to suppression of ATOH1 (a transcription factor instrumental in the differentiation towards a secretory cell type), one of the mechanisms by which NOTCH1 maintains the stem cell in a undifferentiated (self-renewable) state

examples of cross-talk between Notch and with BMP/TGFβ or Wnt signaling pathways